The pathogenetic mechanisms which contribute to the progression of Crohn's disease are still not known. Transforming growth factor-beta (TGF-beta) and its subtypes are multifunctional polypeptides which regulate immunological processes as well as the synthesis of the extracellular matrix and fibrogenesis. In the present study, Crohn's disease tissue samples of 18 patients undergoing intestinal resection were analyzed by Northern blot analysis, in situ hybridization and immunostaining for TGF-beta 1-3 and the TGF-beta receptors type I-III (T beta R-I, T beta R-II, T beta R-III). There was a marked overexpression of TGF-beta 1, TGF-beta 3 and T beta R-II in 94% of the Crohn's disease tissue samples. TGF-beta 2 and T beta R-I ALK5 and T beta R-III were enhanced in 72%, 72% and 82% of the Crohn tissue samples, respectively. In situ hybridization and immunostaining revealed that there was frequent coexpression of TGF-beta with its signaling receptors. Our data indicate that TGF-beta and their receptors seem to be involved in the pathogenesis of Crohn's disease. Their enhanced expression might contribute to the increase in extracellular matrix resulting in fibrosis and subsequently in intestinal obstruction.